BIM deletion polymorphism predicts poor response to EGFR-TKIs in nonsmall cell lung cancer: An updated meta-analysis.

BACKGROUND

A germline deletion in BIM (B cell lymphoma-2-like 11) gene has been shown to impair the apoptotic response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in vitro but its impact on response to EGFR-TKIs in patients of nonsmall cell lung cancer (NSCLC) remains controversial.

METHODS

Eligible literature were searched and screened. Objective response rate (ORR) and disease control rate (DCR) were extracted and aggregated with odds ratio (OR). Hazard ratio (HR) and 95% confidence interval (CI) for progression-free survival (PFS) and overall survival (OS) were extracted and aggregated based on random-effect model.

RESULTS

Fourteen studies including 2694 NSCLC patients were eligible. Individuals harboring BIM deletion polymorphism had inferior ORR (OR = 0.49, 95% CI: 0.34-0.70, P < .001), inferior DCR (OR = 0.50, 95% CI: 0.30-0.84, P = .009). Patients with BIM deletion had shorter OS despite of the heterogeneity between countries (in subgroup of South Korea and Taiwan, HR = 1.34, 95% CI: 1.18-1.53, P < .001; in subgroup of other countries, HR = 2.43, 95% CI: 2.03-2.91, P < .001). The pooled analysis of PFS showed great heterogeneity (I = 79%). All the reported characteristics did not account for the heterogeneity. However, 2 subgroups could be obtained through sensitivity analysis. In one subgroup, patients with BIM deletion polymorphism had shorter PFS (HR = 2.03, 95% CI: 1.71-2.40, P < .001), while in the other subgroup, no significant difference was observed (HR = 0.92, 95% CI: 0.79-1.06, P = .25).

CONCLUSION

NSCLC patients with BIM deletion polymorphism show poor ORR, DCR, and OS after EGFR-TKIs treatment. BIM deletion polymorphism indicates poor response to EGFR-TKIs, and it could be used as a predictor to identify those who would benefit from EGFR-TKIs in NSCLC patients.